Colorectal cancer risk factors
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Editor(s)-in-Chief: C. Michael Gibson, M.S., M.D. [1]Phone:617-632-7753; Elliot B. Tapper, M.D., Beth Israel Deaconess Medical Center
Overview
Colorectal Cancer Risk Factors
There are both genetic and environmental factors that can increase the risk of colorectal carcinoma[1]. FAP and HNPCC are the most common risk factors of CRC, but together these two conditions account for only about 5 percent of CRC[2].
The table below lists the genetic risk factors for colorectal carcinoma:
| Genetic Risk Factor | Description |
| Familial Adenomatous Polyposis (FAP) | AD inheritance; other variants include Gardner's syndrome, Turcot's syndrome, and attenuated adenomatous polyposis coli; caused by germlines mutations in the APC gene[3]; colonic cancer occurs in 90% of untreated individuals around 45 years |
| MUTYH-associated Polyposis (MAP) | AR inheritance; biallelic germline mutations in the base excision repair gene mutY homolog (MYH or MUTYH) |
| Lynch Syndrome AKA Hereditary Non-polyposis Colorectal Cancer (HNPCC) | AD inheritance; defect in one of the mismatch repair genes, most commonly hMLH1, hMSH2, hMSH6, or PMS2; the mean age at initial cancer diagnosis is around 48 years[4] |
The table below lists the environmental risk factors for colorectal carcinoma:
| Environmental Risk Factor | Description |
| Family History | If there is a single affected first-degree relative with CRC; the risk further increases if two first-degree relatives have CRC or the diagnosis was below ages 50-60 years; may have increased risk if a first-degree family member has an adenomatous colonic polyp[5] |
| Personal History | History of CRC or adenomatous polyps, particularly if they are multiple, >1 cm, or villous/tubulovillous[6] |
| Ulcerative Colitis | The increase in risk begins about 8 to 10 years after the initial diagnosis of pancolitis, and at 15 to 20 years for colitis limited to the left colon years; by the fourth decade of disease it reaches as high as 30% in patients with pancolitis; pseudopolyps and strictures may increase the risk[7] |
| Crohn's Disease | There is an increased risk if 1/3 or more of the colonic mucosa is involved |
| Age | The risk of developing CRC increases with age; most cases occur in the 60s and 70s, while cases before age 50 are uncommon unless a family history of early colon cancer is present, cancer in african american individuals tends to occur earlier[8] |
| Abdominal Radiation | Adult survivors of childhood malignancy who received abdominal radiation are at significant risk[9] |
| Race | The African American race has the highest CRC race of all the ethnic groups; the mortality in is 20% higher in the African American race compared to the Caucasian race[10] |
| Gender | CRC mortality is about 25 percent higher in men than in women [11] |
| Acromegaly | Patients with acromegaly are more likely to have multiple adenomatous polyps[12] |
| Renal Transplantation | Renal transplantation, associated with long-term immunosuppression, has been linked with increased CRC risk[13] |
| Diabetes Mellitus and Insulin Resistance | Although it is not clear why but one possible explanation linking diabetes to CRC is hyperinsulinemia; insulin is an important growth factor for colonic mucosal cells and stimulates colonic tumor cells[14] |
| Alcohol | The elevated risk may be related to interference of folate absorption by alcohol and decreased folate intake[15] |
| Obesity | A review of data from 29 studies totaling 37,334 patients reported that each 5 kg/m2 increase in BMI was associated with a 24 percent increased incidence of both colon and rectal cancer in men, and a 9 percent higher incidence of colon cancer in women[15] |
| Cigarette Smoking | A meta-analysis of 106 observational studies estimated that the risk of developing CRC was increased among cigarette smokers compared to those who never smoked; for both incidence and mortality, the association was stronger for cancer of the rectum than the colon[16] |
| Uretercolic Anastomoses | There is increased risk of neoplasia in close proximity to the ureteric stoma[17] |
| Diet | Long-term consumption of red meat or processed meats may be associated with an increased risk of CRC{[18]; diets low in vegetables and high in fats may be associated with increased risk of CRC[19] |
| Coronary Heart Disease | The presence of coronary heart disease has been associated with an increased risk of CRC{[20] |
| Sedentary Lifestyle | Regular exercise stimulates peristalsis, thereby decreasing transit time for carcinogenic substances in the colon[21] |
| Other cancers | Ovarian, endometrial, and breast cancer; there is an increase in risk is more likely if the first primary is diagnosed at an early age[22] |
References
- ↑ Chan AT, Giovannucci EL (2010). "Primary prevention of colorectal cancer". Gastroenterology. 138 (6): 2029–2043.e10. doi:10.1053/j.gastro.2010.01.057. PMC 2947820. PMID 20420944.
- ↑ Burt RW, DiSario JA, Cannon-Albright L (1995). "Genetics of colon cancer: impact of inheritance on colon cancer risk". Annu Rev Med. 46: 371–9. doi:10.1146/annurev.med.46.1.371. PMID 7598472.
- ↑ Mazur IA (1977). "[Synthesis of imidazopyrimidines and imidazoquinazolines with a common nitrogen atom]". Farm Zh (6): 37–41. PMID 598472.
- ↑ Parry S, Win AK, Parry B, Macrae FA, Gurrin LC, Church JM; et al. (2011). "Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery". Gut. 60 (7): 950–7. doi:10.1136/gut.2010.228056. PMC 3848416. PMID 21193451.
- ↑ Winawer SJ, Zauber AG, Gerdes H, O'Brien MJ, Gottlieb LS, Sternberg SS; et al. (1996). "Risk of colorectal cancer in the families of patients with adenomatous polyps. National Polyp Study Workgroup". N Engl J Med. 334 (2): 82–7. doi:10.1056/NEJM199601113340204. PMID 8531963.
- ↑ Atkin WS, Morson BC, Cuzick J (1992). "Long-term risk of colorectal cancer after excision of rectosigmoid adenomas". N Engl J Med. 326 (10): 658–62. doi:10.1056/NEJM199203053261002. PMID 1736104.
- ↑ Ekbom A, Helmick C, Zack M, Adami HO (1990). "Ulcerative colitis and colorectal cancer. A population-based study". N Engl J Med. 323 (18): 1228–33. doi:10.1056/NEJM199011013231802. PMID 2215606.
- ↑ Agrawal S, Bhupinderjit A, Bhutani MS, Boardman L, Nguyen C, Romero Y; et al. (2005). "Colorectal cancer in African Americans". Am J Gastroenterol. 100 (3): 515–23, discussion 514. doi:10.1111/j.1572-0241.2005.41829.x. PMID 15743345.
- ↑ Henderson TO, Oeffinger KC, Whitton J, Leisenring W, Neglia J, Meadows A; et al. (2012). "Secondary gastrointestinal cancer in childhood cancer survivors: a cohort study". Ann Intern Med. 156 (11): 757–66, W-260. doi:10.7326/0003-4819-156-11-201206050-00002. PMC 3554254. PMID 22665813.
- ↑ Jemal A, Siegel R, Xu J, Ward E (2010). "Cancer statistics, 2010". CA Cancer J Clin. 60 (5): 277–300. doi:10.3322/caac.20073. PMID 20610543.
- ↑ Schoenfeld, Philip; Cash, Brooks; Flood, Andrew; Dobhan, Richard; Eastone, John; Coyle, Walter; Kikendall, James W.; Kim, Hyungjin Myra; Weiss, David G.; Emory, Theresa; Schatzkin, Arthur; Lieberman, David (2005). "Colonoscopic Screening of Average-Risk Women for Colorectal Neoplasia". New England Journal of Medicine. 352 (20): 2061–2068. doi:10.1056/NEJMoa042990. ISSN 0028-4793.
- ↑ Delhougne B, Deneux C, Abs R, Chanson P, Fierens H, Laurent-Puig P; et al. (1995). "The prevalence of colonic polyps in acromegaly: a colonoscopic and pathological study in 103 patients". J Clin Endocrinol Metab. 80 (11): 3223–6. doi:10.1210/jcem.80.11.7593429. PMID 7593429.
- ↑ Park JM, Choi MG, Kim SW, Chung IS, Yang CW, Kim YS; et al. (2010). "Increased incidence of colorectal malignancies in renal transplant recipients: a case control study". Am J Transplant. 10 (9): 2043–50. doi:10.1111/j.1600-6143.2010.03231.x. PMID 20883538.
- ↑ Giovannucci E (1995). "Insulin and colon cancer". Cancer Causes Control. 6 (2): 164–79. PMID 7749056.
- ↑ 15.0 15.1 Harnack L, Jacobs DR, Nicodemus K, Lazovich D, Anderson K, Folsom AR (2002). "Relationship of folate, vitamin B-6, vitamin B-12, and methionine intake to incidence of colorectal cancers". Nutr Cancer. 43 (2): 152–8. doi:10.1207/S15327914NC432_5. PMID 12588695.
- ↑ Botteri E, Iodice S, Bagnardi V, Raimondi S, Lowenfels AB, Maisonneuve P (2008). "Smoking and colorectal cancer: a meta-analysis". JAMA. 300 (23): 2765–78. doi:10.1001/jama.2008.839. PMID 19088354.
- ↑ Stewart M, Macrae FA, Williams CB (1982). "Neoplasia and ureterosigmoidostomy: a colonoscopy survey". Br J Surg. 69 (7): 414–6. PMID 7104616.
- ↑ Chao A, Thun MJ, Connell CJ, McCullough ML, Jacobs EJ, Flanders WD; et al. (2005). "Meat consumption and risk of colorectal cancer". JAMA. 293 (2): 172–82. doi:10.1001/jama.293.2.172. PMID 15644544.
- ↑ Glade MJ (1999). "Food, nutrition, and the prevention of cancer: a global perspective. American Institute for Cancer Research/World Cancer Research Fund, American Institute for Cancer Research, 1997". Nutrition. 15 (6): 523–6. PMID 10378216.
- ↑ Chan AO, Jim MH, Lam KF, Morris JS, Siu DC, Tong T; et al. (2007). "Prevalence of colorectal neoplasm among patients with newly diagnosed coronary artery disease". JAMA. 298 (12): 1412–9. doi:10.1001/jama.298.12.1412. PMID 17895457.
- ↑ Lynch BM, Boyle T (2014). "Distinguishing sedentary from inactive: implications for meta-analyses". Br J Cancer. 111 (11): 2202–3. doi:10.1038/bjc.2014.106. PMC 4260011. PMID 24569462.
- ↑ Evans HS, Møller H, Robinson D, Lewis CM, Bell CM, Hodgson SV (2002). "The risk of subsequent primary cancers after colorectal cancer in southeast England". Gut. 50 (5): 647–52. PMC 1773208. PMID 11950810.